Prospects of estrogen receptor β activation in the treatment of castration-resistant prostate cancer
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Julia Gehrig1, Silke Kaulfuß1, Hubertus Jarry2, Felix Bremmer3, Mark Stettner4, Peter Burfeind1 and Paul Thelen5
1Institute of Human Genetics, University Medical Center Goettingen, Germany
2Department of Experimental Endocrinology, University Medical Center Goettingen, Germany
3Institute of Pathology, University Medical Center Goettingen, Germany
4Department of Neurology, University of Essen, Germany
5Department of Urology, University Medical Center Goettingen, Germany
Paul Thelen, email: firstname.lastname@example.org
Keywords: ADT, estrogen receptor β, 8β-VE2, androgen receptor, therapy resistance
Received: July 20, 2016 Accepted: March 08, 2017 Published: March 23, 2017
Advanced prostate cancer can develop into castration-resistant prostate cancer (CRPC). This process is mediated either by intratumoral ligand synthesis or by mutations or aberrations of the androgen receptor (AR) or its cofactors. To date, no curative therapy for CRPC is available, as AR-targeted therapies eventually result in the development of resistance. The human prostate cancer cell line VCaP (vertebral cancer of the prostate) overexpresses AR and its splice variants (ARVs) as a mechanism of resistance to androgen-deprivation therapy (ADT) of external and intratumoral origin. In the present study, we demonstrate that stimulating estrogen receptor β activity with the specific agonist 8β-VE2 in VCaP cells in successive stages of ADT induced a time- and dose-dependent decrease in cell survival and an increase in apoptosis. Furthermore, 8β-VE2 treatment reduced the overexpression of the AR as well as ARVs in VCaP cells under maximum ADT. Our results indicate that decreased survival of the androgen-dependent CRPC cells employing apoptosis together with the regulative effect on AR expression could have beneficial effects over current AR-targeting therapies.
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